A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)

March 21, 2019 updated by: Merck Sharp & Dohme LLC

A Phase II Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients

The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. The primary hypothesis of the study is that the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free survival (PFS) compared to ridaforolimus and exemestane.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to

surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory

  • Post-menopausal
  • With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
  • Has at least one confirmed measurable metastatic lesion
  • Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Has a life expectancy of at least 3 months
  • Adequate organ function

Exclusion Criteria:

  • Is receiving any other concurrent systemic tumor therapy, including

hormonal agents and HER-2 inhibitors

  • Previously received rapamycin or rapamycin analogs, including

ridaforolimus, temsirolimus, or everolimus

  • Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or

other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway

  • Is receiving chronic corticosteroids administered at doses greater than

those used for normal replacement therapy

  • Has active brain metastasis or leptomeningeal carcinomatosis; patients

with adequately treated brain metastases are eligible if they meet certain criteria

  • Known allergy to macrolide antibiotics
  • Has an active infection requiring antibiotics
  • Significant or uncontrolled cardiovascular disease
  • Poorly controlled Type 1 or 2 diabetes
  • Is known to be Human Immunodeficiency Virus (HIV) positive
  • Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are not allowed on this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ridaforolimus + Dalotuzumab + Exemestane
Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, & 22-26 of 28-day cycle.
Other Names:
  • AP23573
  • MK-8669
Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.
Other Names:
  • MK-0646
  • h7C10
Exemestane 25 mg tablet administered PO QD.
Other Names:
  • Aromasin
Active Comparator: Ridaforolimus + Exemestane
Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, & 22-26 of 28-day cycle.
Other Names:
  • AP23573
  • MK-8669
Exemestane 25 mg tablet administered PO QD.
Other Names:
  • Aromasin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16
Time Frame: Baseline, Week 16
The percent change from baseline to Week 16 in the sum of target lesion diameters as determined by anatomic imaging was defined as the line length (i.e., diameter) for each target lesion identified at baseline summed across all lesions at baseline, and separately at each post-baseline time point. The primary analysis was conducted using a constrained longitudinal data analysis (cLDA) method and target lesion measurements according to the BICR. Percent change from baseline in sum of target lesion diameters at Week 16 was reported for each treatment arm.
Baseline, Week 16
3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
ORR was defined as the percentage of participants whose best response was complete response (CR; disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or partial response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR. ORR was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.
From Day 1 through last post-study efficacy follow-up (up to ~19 months)
Overall Survival (OS)
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date last known to be alive. OS was analyzed using the Kaplan-Meier method and median OS (95% confidence interval [CI]) in weeks was reported for each treatment arm. Per protocol, all participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 4, 2012

Primary Completion (Actual)

February 19, 2014

Study Completion (Actual)

March 15, 2018

Study Registration Dates

First Submitted

May 22, 2012

First Submitted That Met QC Criteria

May 22, 2012

First Posted (Estimate)

May 24, 2012

Study Record Updates

Last Update Posted (Actual)

March 25, 2019

Last Update Submitted That Met QC Criteria

March 21, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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